Mimotopes (mimetics or mimics) are molecules that mimic the function of other, naturally-occurring molecules by virtue of having the same shape (topography) and size as a fragment of/or of the interacting region of naturally-occurring molecules that they are mimicking. A method for determining mimotopes is described in U.S. Pat. No. 4,833,092 (Geysen).
As shown in FIG. 1a, a natural ligand has a particular shape and size that enables it to bind to a natural receptor. A mimotope ligand is a molecule that mimics the shape of the natural ligand and thus mimics its functional ability to bind to a natural receptor, as shown in FIG. 1b. In other words, a mimotope ligand is a molecule that is the topographical equivalent of a natural ligand (at least in terms of their binding surfaces) so as to be complementary to a particular receptor of interest.
A variety of ligand mimics are known in the art, which are used primarily as inhibitors or blockers, e.g. U.S. Pat. No. 4,550,163 (Voss et al.) entitled “Ligand analog-irreversible enzyme inhibitor conjugates” and U.S. Pat. No. 6,139,832 (Li et al.) entitled “Leukocyte adhesion inhibitor-1 (LAI-1) Polypeptides”. Small peptides are also known as protein mimetics (see, e.g. Wrighton et al., “Small Peptides as Potent Mimetics of the Protein Hormone Erythropoietin” in Science (1996 Jul. 26; 273(5274):458-64). Mimetics of polypeptides used to detect antibodies are described in U.S. Pat. No. 6,858,210 (Marquis et al.). Peptide mimics for backbone-to-backbone or backbone-to-chain cyclizations are described in U.S. Pat. No. 6,706,862 (Hornik).
In the context of platelets, mimotopes are also known as inhibitors of platelet adhesion and aggregation, such as described in U.S. Pat. No. 5,114,842 (Plow et al.) entitled “Peptides and Antibodies that Inhibit Platelet Adhesion”. Specifically, Plow et al. teach a polypeptide analog capable of immunologically mimicking a linear hGPIIb antigenic determinant expressed when platelet-associated GPIIb-IIIa binds fibrinogen. Both U.S. Pat. No. 5,817,748 (Miller et al.) and its Continuation-in-Part U.S. Pat. No. 5,877,155 describe mimotopes and anti-mimotopes of human platelet glycoprotein IB/IX as well as a method for modulating platelet adhesion, aggregation or agglutination by exposing the platelets to an anti-mimotope in order to inhibit von Willebrand factor interaction with platelets through the glycoprotein Ib/IX complex receptor. However, these ligand mimics only perform an inhibitory (antithrombotic) function.
Although the foregoing represent useful advances in the art, further advances in platelet and antithrombotic technology remain highly desirable.